Umbilical cord-matrix stem cells induce the functional restoration of vascular endothelial cells and enhance skin wound healing in diabetic mice via the polarized macrophages

Abstract Background: Full-thickness wounds are a serious problem which badly affects patients’ life quality and also become the difficult problem for clinicians. Stem cells have great prospects in the treatment of wounds. Our previous experiments proved that autologous basal cell suspension can promote wound healing, and there are epidermal stem cells (ESCs) in basal cell suspension. We then conducted experiments to explore the effect of ESCs on full-thickness wound. Methods: In our study, the rat ESCs were isolated and expanded, and transfected with lentivirus to stably express EGFP. Experimental rats were randomly divided into 2 groups, in the ESCs group, the rat ESCs were sprayed on the Full-thickness wounds of the rats, while in control group, sprayed the PBS on the wound. Wound healing and neovascularization were then evaluated. Colonization, division and differentiation of ESCs on the wound were discovered by immunofluorescence.Results: The result suggested that rat ESCs can colonize, divide and proliferate in the wound. What’s more, the rat ESCs around blood vessels can differentiate into vascular endothelial cells and form a lumen-like structure. Compared with the control group, spraying the rat ESCs on the wound bed can promote angiogenesis and accelerate wound healing. Conclusions: Our study proved that rat ESCs were safe and effective for treating full-thickness wounds, and under certain conditions, ESCs can differentiate into vascular endothelial cells to promote angiogenesis and wound healing.

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Rat epidermal stem cells promote the angiogenesis of full-thickness wound

10.21203/rs.3.rs-28767/v2 ◽

2020 ◽

Author(s):

Shaobin Huang ◽

Zhicheng Hu ◽

Peng Wang ◽

Yi zhang ◽

Xiaoling Cao ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Endothelial Cells ◽

Cell Suspension ◽

Basal Cell ◽

Vascular Endothelial Cells ◽

Control Group ◽

Vascular Endothelial ◽

Epidermal Stem Cells ◽

Full Thickness

Abstract Background: Full-thickness wounds severely affect patients’ life quality and become challenging problems for clinicians. Stem cells have great prospects in the treatment of wounds. Our previous study confirmed that autologous basal cell suspension could promote wound healing, and epidermal stem cells (ESCs) were detected in the basal cell suspension. Herein, this study aimed to explore the effect of ESCs on full-thickness wounds. Methods: Rat ESCs were isolated and expanded, and then were transfected with lentivirus to stably express enhanced green fluorescent protein. The experimental rats were randomly divided into 2 groups: in the ESC group, the rat ESCs were sprayed on the full-thickness wounds of rats; in the control group, phosphate-buffered saline was sprayed the on the wounds. Next, wound healing and neovascularization were evaluated. Colonization, division and differentiation of ESCs on the wound were analyzed by immunofluorescence. Results: The rat ESCs colonized, divided and proliferated in the wound. Additionally, rat ESCs around blood vessels differentiated into vascular endothelial cells and formed a lumen-like structure. Compared with the control group, the ESC group showed enhanced angiogenesis and accelerated wound healing. Conclusions: Our study confirmed that rat ESCs are safe and effective for treating full-thickness wounds . Additionally, under certain conditions, ESCs can differentiate into vascular endothelial cells to promote angiogenesis and wound healing.

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Autocrine and Paracrine Effects of Vascular Endothelial Cells Promote Cutaneous Wound Healing

BioMed Research International ◽

10.1155/2021/6695663 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yang Lu ◽

Yuhao Yang ◽

Liling Xiao ◽

Shenghong Li ◽

Xuan Liao ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Endothelial Cells ◽

Endothelial Cell ◽

Growth Factor ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Biological Behaviour ◽

And Migration ◽

Proliferation And Migration

Background. When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing. Materials and Methods. ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31. Results. HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing. Conclusion. Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.

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Actions of Liraglutide on Vascular Endothelial Cells Play a Central Role in the Suppression of Atherosclerosis in Diabetic Mice

Diabetes ◽

10.2337/db18-487-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 487-P

Author(s):

MUNENORI HIROMURA ◽

YUSAKU MORI ◽

MASAKAZU KOSHIBU ◽

HIDEKI KUSHIMA ◽

KYOKO KOHASHI ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Diabetic Mice

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The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽

10.3390/nano11020457 ◽

2021 ◽

Vol 11 (2) ◽

pp. 457

Author(s):

Andreu Blanquer ◽

Jana Musilkova ◽

Elena Filova ◽

Johanka Taborska ◽

Eduard Brynda ◽

...

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Chronic Wounds ◽

Human Keratinocytes ◽

Skin Wound ◽

Platelet Lysate ◽

Therapeutic Approaches ◽

Skin Wound Healing ◽

New Therapeutic Approaches ◽

Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽

10.3390/molecules26092554 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2554

Author(s):

Marek Konop ◽

Anna K. Laskowska ◽

Mateusz Rybka ◽

Ewa Kłodzińska ◽

Dorota Sulejczak ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Diabetic Mice ◽

Full Thickness ◽

Skin Wound Healing ◽

Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

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